Researchers have used radio immunotherapy to destroy remaining human immunodeficiency virus-infected cells in the blood samples of patients treated with antiretroviral therapy.

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Researchers have used radio immunotherapy (RIT) to destroy
remaining human immunodeficiency virus (HIV)-infected cells in the blood
samples of patients treated with antiretroviral
therapy, offering the promise of a strategy for curing HIV infection.

Results of the study
were presented at the annual meeting of the Radiological Society of North
America (RSNA).

Highly active antiretroviral therapy (HAART) has transformed
the outlook for patients infected with HIV by suppressing the replication of
the virus in the body. However, despite the success of HAART in effectively
reducing the burden of HIV, scientists believe reservoirs of latently infected
cells persist in the body, preventing the possibility of a permanent cure.

"In an HIV patient on HAART, drugs suppress viral
replication, which means they keep the number of viral particles in a patient's
bloodstream very low. However, HAART cannot kill the HIV-infected cells,"
said the study's lead author, Ekaterina Dadachova, PhD, professor of radiology,
microbiology and immunology at Albert Einstein College of Medicine in the
Bronx, New York. "Any strategy for curing HIV infection must include a method to
eliminate viral-infected cells."

The use of antibodies

In her study, Dr Dadachova and a team of researchers
administered RIT to blood samples from 15 HIV patients treated with HAART at
the Einstein-Montefiore Centre for Aids Research.

RIT, which has historically been employed to treat cancer,
uses monoclonal
antibodies – cloned cells that are recruited by the immune system to identify
and neutralise antigens.
Antigens are foreign objects like bacteria and viruses that stimulate an immune
response in the body.

The antibody, designed to recognise and bind to a specific
cell antigen, is paired with a radioactive isotope. When injected into the
patient's bloodstream, the laboratory-developed antibody travels to the target
cell where the radiation is then delivered.

"In RIT, the antibodies bind to the infected cells and
kill them by radiation," Dr Dadachova said. "When HAART and RIT are
used together, they kill the virus and the infected cells, respectively."

For the study, Dr Dadachova's team paired the monoclonal
antibody (mAb2556) designed to target a protein expressed on the surface of
HIV-infected cells with the radionuclide Bismuth-213.

Undetectable levels

The researchers found that RIT was able to kill HIV-infected
lymphocytes previously treated with HAART, reducing the HIV infection in
the blood samples to undetectable levels.

"The elimination of HIV-infected cells with RIT was
profound and specific," Dr Dadachova said. "The radionuclide we used
delivered radiation only to HIV-infected cells without damaging nearby
cells."

An important part of the study tested the ability of the
radiolabelled antibody to reach HIV-infected cells in the brain and central
nervous system. Using an in vitro human blood brain barrier model, the
researchers demonstrated that radiolabelled mAb2556 could cross the blood
brain barrier and kill HIV-infected cells without any overt damage to the
barrier itself.

"Antiretroviral treatment only partially penetrates the
blood brain barrier, which means that even if a patient is free of HIV
systemically, the virus is still able to rage on in the brain, causing cognitive
disorders and mental decline," Dr Dadachova said. "Our study
showed that RIT is able to kill HIV-infected cells both systemically and within
the central nervous system."

According to Dr Dadachova, clinical trials in HIV patients
are the next step for the RIT treatment.

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